Prostate cancer is one of the most common cancers among elder men (1). Prostate cancer frequently metastasizes to bone, and androgen withdrawal therapy has been applied for such patients. However, there is no efficient therapy against hormone-refractory and metastatic prostate cancer. Therefore, there is an urgent need for the development of new therapeutic modalities, and specific immunotherapy is one candidate. Indeed, prostate tissue-specific antigens expressed in the normal prostate can be target molecules for specific immunotherapy (2). Specific immunotherapy targeting prostate tissue-specific antigens has been carried out, and, in recent years, the inventors have identified several epitope peptides derived from prostate-related antigens that are able to generate prostate cancer-reactive cytotoxic T lymphocytes (CTLs) from prostate cancer patients (23–26). However, one major obstacle encountered when treating prostate cancer patients is the treatment of bone metastases, as prostate cancer frequently metastasizes to the bone tissue (1). Thus, the clinical responses remain unsatisfactory (3–7).
Enhancer of zeste homolog 2 (EZH2) is a polycomb group protein homologous to the Drosophila enhancer of zeste, and is involved in gene silencing (8). Dysregulation of this gene-silencing machinery can lead to cancer (9–11). In addition, it has been reported that EZH2 is overexpressed in metastatic prostate cancer and functions as a transcriptional repressor, and that inhibition of EZH2 blocks growth of prostate cancer cells (12).
In our clinical trials against several types of cancer, several class I-binding cancer antigen-derived peptides that had originally been identified by their ability to induce cancer-reactive CTLs were also recognized by immunoglobulin G (IgG) (13, 14). Additional clinical trials revealed that the induction of IgG reactive to administered peptides was positively correlated with the overall survival of cancer patients (15–17). These lines of evidence suggest that peptides that can be recognized by both the humoral and cellular immune systems might be more useful for immunotherapy than peptides that can be recognized by only one of the two systems. In addition, the assay for peptide-specific IgG is much simpler and easier than the in vitro sensitization experiment to induce peptide-specific CTLs (18).